The Genomic Organization of Plant Pathogenicity in Fusarium Species Martijn Rep1 and H Corby Kistler2

Total Page:16

File Type:pdf, Size:1020Kb

The Genomic Organization of Plant Pathogenicity in Fusarium Species Martijn Rep1 and H Corby Kistler2 Available online at www.sciencedirect.com The genomic organization of plant pathogenicity in Fusarium species Martijn Rep1 and H Corby Kistler2 Comparative genomics is a powerful tool to infer the molecular cation and genetic transmission. We here highlight recent basis of fungal pathogenicity and its evolution by identifying insights into the evolution of disease-causing ability differences in gene content and genomic organization between among plant pathogenic fungi, focusing on the compara- fungi with different hosts or modes of infection. Through tive genomic analysis of Fusarium species with additional comparative analysis, pathogenicity-related chromosomes reference to other fungi. have been identified in Fusarium oxysporum and Fusarium solani that contain genes for host-specific virulence. Lateral Comparative genomics transfer of pathogenicity chromosomes, inferred from genomic In 2007 the Broad Institute released its first Fusarium data, now has been experimentally confirmed. Likewise, comparativegenomicswebsite(http://www.broadinstitute. comparative genomics reveals the evolutionary relationships org/annotation/genome/fusarium_group/MultiHome. among toxin gene clusters whereby the loss and gain of genes html), which brought together high quality sequence from the cluster may be understood in an evolutionary context assemblies of the plant pathogenic fungus Fusarium grami- of toxin diversification. The genomic milieu of effector genes, nearum, sequenced previously [1] and two new WGS for encoding small secreted proteins, also suggests mechanisms the species Fusarium verticillioides and Fusarium oxysporum. that promote genetic diversification for the benefit of the At the sametime,theJoint Genome Institute (JGI) released pathogen. a WGS for Fusarium solani (Nectria haematococca)(http:// Addresses genome.jgi-psf.org/Necha2/Necha2.home.html). The four 1 Plant Pathology, Swammerdam Institute for Life Sciences, Faculty of genomes share considerable sequence similarity as well as Science, University of Amsterdam, P.O. Box 94215, 1090 GE extensive synteny (Figure 1)[2,3]. Amsterdam, The Netherlands 2 USDA ARS Cereal Disease Laboratory, 1551 Lindig St., University of Minnesota, St. Paul, MN 55108, USA The Fusarium genomes consist of a core region with approximately 9000 genes considered to be orthologous Corresponding authors: Rep, Martijn ([email protected]) and Kistler, H Corby due to high sequence similarity and conserved gene order ([email protected]) [3]. Each species also contains thousands of genes that are unique to each genome, many of which are found near Current Opinion in Plant Biology 2010, 13:420–426 the ends of chromosomes. In F. graminearum, these tel- omere proximal regions are rich in gene diversity as This review comes from a themed issue on measured by SNP density [1] and are regions of elevated Biotic interactions Edited by Jane E. Parker and Jeffrey G. Ellis recombination [4]. Distinctively, F. graminearum also contains interstitial chromosomal regions of high diversity Available online 13th May 2010 and recombination that appear to have been created by an 1369-5266/$ – see front matter ancestral telomeric fusion of chromosomes [1 ,3 ]. How Published by Elsevier Ltd. these interstitial regions of F. graminearum chromosomes have maintained high genetic diversity, normally associ- DOI 10.1016/j.pbi.2010.04.004 ated with telomeres, remains a mystery. Comparative genomics with closely related Aspergillus Introduction species also has revealed large species-specific gene sets, Genomic sequencing of fungal phytopathogens has revo- which are concentrated in subgenomic regions called lutionized the study of plant pathogenesis. Whole gen- chromosomal islands [5 ]. Interestingly, these regions ome sequence (WGS) data for individual fungal genomes have a subtelomeric bias too. This could be due to the accelerated classical forward and reverse genetic inherent recombinogenic nature of chromosome ends but approaches for identifying pathogenicity genes. More seems to have functional implications as well; subtelo- recently, the availability of several WGS assemblies for meric gene expression is associated with invasive growth comparative genomic analysis has enabled unprece- of Aspergillus fumigatus in mammals and ex vivo neutrophil dented opportunities for tracing the evolutionary origin exposure [6]. (and demise) of genes and molecules that influence the outcome of fungal–plant interactions. Moreover, the over- Instead of genomic islands, both F. oxysporum and F. all genomic organization of fungal pathogenicity-related solani contain supernumerary chromosomes that largely genes has suggested novel modes of molecular diversifi- consist of lineage-specific sequences and make up a Current Opinion in Plant Biology 2010, 13:420–426 www.sciencedirect.com Genomic organization of plant pathogenicity in Fusarium species Rep and Kistler 421 Figure 1 Comparison of Fusarium Genomes. Synteny of the F. oxysporum, F. verticillioides, F. graminearum,andF. solani genomes determined by BLASTN alignment (cutoff 1e-10). Chromosomes (Chr) of F. oxysporum are used as a reference and the scale (bottom) measures chromosome size in megabases (Mb). Grey boxes indicate chromosome size determined by optical mapping, upon which are superimposed corresponding WGS assembly scaffolds displayed as numbered black bars. Unassembled scaffolds (Un) are concatenated for ease of display. Regions of shared gene order with chromosomes of F. verticillioides, F. graminearum and F. solani, are shown beneath each F. oxysporum chromosome. Sequences from individual chromosomes in each species are color-coded so that blocks of solid color represent regions of synteny with the F. oxysporum genome. Little homology or synteny is apparent for the lineage specific regions of F. oxysporum chromosomes 3, 6, 14 and 15 and for telomere-proximal portions of chromosomes 1 and 2. Figure modified from supplemental material of [3]. www.sciencedirect.com Current Opinion in Plant Biology 2010, 13:420–426 422 Biotic interactions substantial fraction of the entire genome [2,3]. Lin- co-cultivation, resulting in a new pathogenic lineage. eage-specific portions of F. oxysporum and F. solani are Lateral chromosome transfer, first observed in Colleto- highly enriched in transposable elements. Regions of high trichum gloeosporioides [17], likely explains the existence genome diversity in Fusarium, whether at chromosome of host-specific groups of strains ( formae speciales)ofF. ends, special interstitial sites or on supernumerary oxysporum composed of several independent lineages. chromosomes, also have been shown to be rich in genes This is supported by the observation that the sequences predicted to be involved in fungal–host interactions. High of the effector genes on the pathogenicity chromosome diversity regions are enriched for predicted secreted are, with few exceptions, identical between disparate proteins, carbohydrate-active enzymes and genes specifi- lineages and highly specific to lineages which are patho- cally expressed during plant infection [1,3,7]. genic to tomato [18]. Effector genes, pathogenicity chromosomes In the pea-pathogenic form of F. solani, supernumerary and horizontal transfer chromosomes also harbor genes for host-specific viru- Effectors are proteins secreted by pathogens that promote lence, including detoxification mechanisms and host virulence, commonly by interacting with plant host nutrient utilization [19,20]. Three supernumerary proteins [8]. Because of these interactions, effector genes chromosomes with sizes between 0.5 and 1.6 Mb have are frequently involved in molecular arms races between characteristics that distinguish them from the rest of the pathogen and plant and subject to accelerated evolution genome including higher levels of repeat sequences [9]. The location of effector genes in a genome may affect (mostly transposons), more duplicated and unique genes, the rate at which they evolve through mutation or recom- smaller average gene size and a lower G+C content. Like bination. In Leptosphaeria maculans, for instance, the in F. oxysporum, sequences of the genes on these chromo- effector (Avr) genes that have been identified through somes suggest activities consistent with habitat special- positional cloning all reside in AT-rich genomic subre- ization but no involvement in essential cellular functions gions of up to several hundred kb consisting mostly of [2]. For Alternaria alternata, too, host plant-specific remnants of retrotransposons [10,11,12]. These long pathogenicity can be attributed to supernumerary chromosomal segments of uniform AT/GC content are chromosomes, of 1.0–1.7 Mb [21]. Genes for synthesis similar to isochores found in other eukaryotes. of host-selective toxins that are crucial for host-specificity are located on these chromosomes [22]. Although these highly particular, isochore-like genomic subregions presently have been found only in L. maculans, Transposons the genomic location of effector genes is also non-random Could the proximity of effector genes to repeats or in several other fungi. In the corn pathogen Ustilago transposons accelerate their evolution? While Lepto- maydis, a significant fraction (18%) of the genes for sphaeria represents an extreme case of repetitive genomic secreted proteins are organized in 12 clusters (3–26 genes context of effector genes, the context of effector genes in per cluster) dispersed in the genome [13]. Most clusters other fungi is also often transposon rich [16,23]. In contain tandem arrays of 2–5
Recommended publications
  • The Genomic Organization and Expression Pattern of the Low-Affinity Fc Gamma Receptors (Fcγr) in the Göttingen Minipig
    Immunogenetics (2019) 71:123–136 https://doi.org/10.1007/s00251-018-01099-1 ORIGINAL ARTICLE The genomic organization and expression pattern of the low-affinity Fc gamma receptors (FcγR) in the Göttingen minipig Jerome Egli1 & Roland Schmucki1 & Benjamin Loos1 & Stephan Reichl1 & Nils Grabole1 & Andreas Roller1 & Martin Ebeling1 & Alex Odermatt2 & Antonio Iglesias1 Received: 9 August 2018 /Accepted: 24 November 2018 /Published online: 18 December 2018 # The Author(s) 2018 Abstract Safety and efficacy of therapeutic antibodies are often dependent on their interaction with Fc receptors for IgG (FcγRs). The Göttingen minipig represents a valuable species for biomedical research but its use in preclinical studies with therapeutic antibodies is hampered by the lack of knowledge about the porcine FcγRs. Genome analysis and sequencing now enabled the localization of the previously described FcγRIIIa in the orthologous location to human FCGR3A. In addition, we identified nearby the gene coding for the hitherto undescribed putative porcine FcγRIIa. The 1′241 bp long FCGR2A cDNA translates to a 274aa transmembrane protein containing an extracellular region with high similarity to human and cattle FcγRIIa. Like in cattle, the intracellular part does not contain an immunoreceptor tyrosine-based activation motif (ITAM) as in human FcγRIIa. Flow cytometry of the whole blood and single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) of Göttingen minipigs revealed the expression profile of all porcine FcγRs which is compared to human and mouse. The new FcγRIIa is mainly expressed on platelets making the minipig a good model to study IgG-mediated platelet activation and aggregation. In contrast to humans, minipig blood monocytes were found to express inhibitory FcγRIIb that could lead to the underestimation of FcγR-mediated effects of monocytes observed in minipig studies with therapeutic antibodies.
    [Show full text]
  • Chain Locus Heavy Genomic Organization of the Variable
    Antibody Repertoire Development in Fetal and Neonatal Piglets. XI. The Relationship of Variable Heavy Chain Gene Usage and the Genomic Organization of the Variable Heavy This information is current as Chain Locus of September 27, 2021. Tomoko Eguchi-Ogawa, Nancy Wertz, Xiu-Zhu Sun, Francois Puimi, Hirohide Uenishi, Kevin Wells, Patrick Chardon, Gregory J. Tobin and John E. Butler J Immunol published online 5 March 2010 Downloaded from http://www.jimmunol.org/content/early/2010/03/05/jimmun ol.0903616 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2010/03/05/jimmunol.090361 Material 6.DC1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 27, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts Errata An erratum has been published regarding this article. Please see next page or: /content/190/3/1383.full.pdf The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published March 5, 2010, doi:10.4049/jimmunol.0903616 The Journal of Immunology Antibody Repertoire Development in Fetal and Neonatal Piglets.
    [Show full text]
  • Genomic Insights Into Drug Resistance Determinants in Cedecea Neteri, a Rare Opportunistic Pathogen
    microorganisms Article Genomic Insights into Drug Resistance Determinants in Cedecea neteri, A Rare Opportunistic Pathogen Dorothea K. Thompson * and Stephen M. Sharkady Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, Campbell University, Buies Creek, NC 27506, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-910-893-7463 Abstract: Cedecea, a genus in the Enterobacteriaceae family, includes several opportunistic pathogens reported to cause an array of sporadic acute infections, most notably of the lung and bloodstream. One species, Cedecea neteri, is associated with cases of bacteremia in immunocompromised hosts and has documented resistance to different antibiotics, including β-lactams and colistin. Despite the potential to inflict serious infections, knowledge about drug resistance determinants in Cedecea is limited. In this study, we utilized whole-genome sequence data available for three environmental strains (SSMD04, M006, ND14a) of C. neteri and various bioinformatics tools to analyze drug resistance genes in this bacterium. All three genomes harbor multiple chromosome-encoded β-lactamase genes. A deeper analysis of β-lactamase genes in SSMD04 revealed four metallo-β-lactamases, a novel variant, and a CMY/ACT-type AmpC putatively regulated by a divergently transcribed AmpR. Homologs of known resistance-nodulation-cell division (RND)-type multidrug efflux pumps such as OqxB, AcrB, AcrD, and MdtBC were also identified. Genomic island prediction for SSMD04 indicated that tolC, involved in drug and toxin export across the outer membrane of Gram-negative bacteria, Citation: Thompson, D.K.; Sharkady, was acquired by a transposase-mediated genetic transfer mechanism. Our study provides new S.M. Genomic Insights into Drug insights into drug resistance mechanisms of an environmental microorganism capable of behaving as Resistance Determinants in Cedecea a clinically relevant opportunistic pathogen.
    [Show full text]
  • Human J3 Satellite
    Proc. Nati. Acad. Sci. USA Vol. 86, pp. 6250-6254, August 1989 Genetics Human j3 satellite DNA: Genomic organization and sequence definition of a class of highly repetitive tandem DNA (human genome/concerted evolution/acrocentric chromosomes) JOHN S. WAYE AND HUNTINGTON F. WILLARD* Department of Medical Genetics, University of Toronto, Toronto, ON M5S 1A8 Canada Communicated by Charles R. Cantor, May 15, 1989 (receivedfor review August 23, 1988) ABSTRACT We describe a class ofhuman repetitive DNA, In this report, we describe the isolation and characteriza- called (3 satellite, that, at a most fundamental level, exists as tion of a human satellite DNA family, f satellitet which is tandem arrays of diverged -68-base-pair monomer repeat unrelated in structure or sequence to any previously de- units. The monomer units are organized as distinct subsets, scribed human satellite DNAs. These sequences comprise a each characterized by a multimeric higher-order repeat unit minimum of several million base pairs of DNA in the human that is tandemly reiterated and represents a recent unit of genome and are organized, at a fundamental level, as tandem amplification. We have cloned, characterized, and determined arrays of diverged -68-bp monomer repeat units. The P the sequence of two (3 satellite higher-order repeat units: one satellite DNA family is subdivided into two or more distinct located on chromosome 9, the other on the acrocentric chro- subsets, at least one of which is shared by the five pairs of mosomes (13, 14, 15, 21, and 22) and perhaps other sites in the acrocentric chromosomes. genome. Analysis by pulsed-field gel electrophoresis reveals that these tandem arrays are localized in large domains (50-300 MATERIALS AND METHODS kilobase pairs) that are marked by restriction fragment length polymorphisms.
    [Show full text]
  • Laboratory Genetics and Genomics Learning Guide
    American Board of Medical Genetics and Genomics Learning Guide for Laboratory Genetics and Genomics May 2016 INTRODUCTION: These learning guides have been developed by the ABMGG to assist training program directors and trainees as they design, implement, monitor and evaluate the educational content of their ABMGG accredited training programs. The format of these learning guides reflects the common areas of knowledge and training that have been developed by the medical profession across the training spectra and that are often referred to as the “Six Competencies.” The ABMGG has taken these areas of knowledge and experience and translated them into more specific content areas for ABMGG accredited programs. These learning guides are not presumed to be inclusive or exclusive. Thus you will find that they mirror many other guiding principle documents from within the genetics community. Similarly, while they attempt to cover as many specific areas of training as possible, they cannot be viewed as the only areas of knowledge and expertise that are required to become a successful medical genetics professional. They are, as indicated, learning guides; and are not rules or testing outlines. These guides are offered to the medical genetics educational community as one source of information concerning knowledge areas that may be useful in developing and evaluating the educational content of training programs. Domain Objectives Skills 1. Patient care Pre-analytic laboratory Identify appropriate specimens for Select appropriate containers, anticoagulants, collection media, antibiotics, and skills study, and methods of collection, preservatives for validated specimen type. preservation, and transport Identify factors important for the transport of specimens, such as overnight delivery, transport media and containers, recommended temperatures.
    [Show full text]
  • Precision Medicine Informatics: Principles, Prospects, and Challenges
    Received October 22, 2019, accepted December 26, 2019, date of publication January 13, 2020, date of current version January 23, 2020. Digital Object Identifier 10.1109/ACCESS.2020.2965955 Precision Medicine Informatics: Principles, Prospects, and Challenges MUHAMMAD AFZAL 1, (Member, IEEE), S. M. RIAZUL ISLAM 2, (Member, IEEE), MAQBOOL HUSSAIN 1, AND SUNGYOUNG LEE 3, (Member, IEEE) 1Department of Software, Sejong University, Seoul 05006, South Korea 2Department of Computer Science and Engineering, Sejong University, Seoul 05006, South Korea 3Department of Computer Science and Engineering, Kyung Hee University, Yongin 17104, South Korea Corresponding author: Sungyoung Lee ([email protected]) This work was supported in part by the Ministry of Science and ICT (MSIT), South Korea, through the Information Technology Research Center (ITRC) Support Program under Grant IITP-2017-0-01629, and in part by the Institute for Information & Communications Technology Promotion (IITP), through the Korea Government (MSIT) under Grant 2017-0-00655 and Grant NRF-2019R1A2C2090504. ABSTRACT Precision medicine (PM) is an emerging approach that appears with the impression of changing the existing paradigm of medical practice. Recent advances in technological innovations and genetics and the growing availability of health data have set a new pace of the research and impose a set of new requirements on the different stakeholders. Some studies are available that discuss about the different aspects of PM. Nevertheless, a holistic representation of those aspects deemed to confer with the technological perspective, in relation to the applications and challenges, have been mostly ignored. In this context, this paper surveys the advances in PM from the informatics viewpoint and reviews the enabling tools and techniques in a categorized manner.
    [Show full text]
  • Genomic Organization
    Proc. Nati. Acad. Sci. USA Vol. 85, pp. 4218-4222, June 1988 Biochemistry Primary structure of the human follistatin precursor and its genomic organization (ovary/testis/pituitary/prehormone/alternative splicing) SHUNICHI SHIMASAKI*, MAKOTO KOGA*, FREDERICK ESCHt, KAREN COOKSEY*, MALUZ MERCADO*, ANN KOBA*, NAOTO UENO*, SHAO-YAO YING*, NICHOLAS LING*, AND ROGER GUILLEMIN* *Laboratories for Neuroendocrinology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037; and tAthena Neurosciences, Inc., 887-D Industrial Road, San Carlos, CA 94070 Contributed by Roger Guillemin, February 23, 1988 ABSTRACT Follistatin is a single-chain gonadal protein characterized porcine inhibins A and B. By use ofthe porcine that specifically inhibits follicle-stimulating hormone release. cDNA as a probe, we report herein the cloning and sequenc- By use ofthe recently characterized porcine follistatin cDNA as ing of the human follistatin precursor as well as the deter- a probe to screen a human testis cDNA library and a genomic mination of its genomic organizationA library, the structure of the complete human follistatin pre- cursor as well as its genomic organization have been deter- mined. Three of eight cDNA clones that were sequenced MATERIALS AND METHODS predicted a precursor with 344 amino acids, whereas the Cloning and DNA Sequencing. An oligo(dT)-primed human remaining five cDNA clones encoded a 317 amino acid precur- testicular cDNA library constructed with the vector Agtll sor, resulting from alternative splicing ofthe precursor mRNA. was purchased from Clontech (Palo Alto, CA). The mRNA Mature follistatins contain four contiguous domains that are used to produce the library was derived from the testis of a encoded by precisely separated exons; three of the domains are healthy 50-year-old man.
    [Show full text]
  • A Genetic Revolution in Rare-Disease Medicine
    News & views These large swathes of repetitive DNA come Karen H. Miga is at the UC Santa Cruz 8. Koren, S. et al. Nature Biotechnol. 30, 693–700 with different sets of rules, in terms of their Genomics Institute, University of California, (2012). 9. Jain, M. et al. Nature Biotechnol. 36, 338–345 (2018). genomic organization and evolution. They are Santa Cruz, California 95064, USA. 10. Jain, M. et al. Nature Biotechnol. 36, 321–323 (2018). also subject to different epigenetic regulation e-mail: [email protected] 11. Chaisson, M. J. P. et al. Nature 517, 608–611 (2015). (molecular modifications to DNA and associ- 12. Wenger, A. M. et al. Nature Biotechnol. 37, 1155–1162 (2019). ated proteins that do not alter the underlying 13. Nurk, S. et al. Genome Res. 30, 1291–1305 (2020). DNA sequence), which leads repetitive DNA to 14. Bzikadze, A. V. & Pevzner, P. A. Nature Biotechnol. 38, 1. International Human Genome Sequencing Consortium. differ from euchromatin in terms of its organ- 1309–1316 (2020). Nature 409, 860–921 (2001). 15. Zentner, G. E., Saiakhova, A., Manaenkov, P., Adams, M. D. ization, replication timing and transcriptional 2. Venter, J. C. et al. Science 291, 1304–1351 (2001). & Scacheri, P. C. Nucleic Acids Res. 39, 4949–4960 activity17–19. Many genome-wide tools and data 3. Schneider, V. A. et al. Genome Res. 27, 849–864 (2017). (2011). 4. Miga, K. H. et al. Nature 585, 79–84 (2020). 16. Schueler, M. G., Higgins, A. W., Rudd, M. K., Gustashaw, K. sets cannot yet fully capture all this informa- 5.
    [Show full text]
  • Immunology Research Review an Overview of Recent Immunology Research Publications Featuring Illumina® Technology CONTENTS
    Immunology Research Review An Overview of Recent Immunology Research Publications Featuring Illumina® Technology CONTENTS 4 Introduction 6 Adaptive immunity Repertoire Sequencing of Lymphocyte Receptors Single-Cell Repertoire Sequencing 13 Lymphocyte Development T Cell Development B Cell Development 18 Innate Immunity 20 Cancer and the Immune Response 21 Microbiota and the Immune System 24 Major Histocompatibility Complex Phase-Defined HLA Sequencing 29 Self vs Non-Self Antigen Discrimination Tolerance Autoimmunity Solid Organ Transplantation 36 Infectious Diseases and Vaccines Viral Infections Vaccine Development 41 Techniques miRNA and noncoding RNAs ChIP-Seq 46 Biblography This document highlights recent publications that demonstrate the use of Illumina technologies in immunology research. To learn more about the platforms and assays cited, visit www.illumina.com. An Overview of Publications Featuring Illumina® Technology 3 INTRODUCTION Immunology is the field of study concerned with the recognition and disposal of 1. Neller M. A., Burrows J. M., Rist M. J., Miles foreign or “non-self” material that enters the body. This material is usually in the J. J. and Burrows S. R. (2013) High frequency form of life-threatening infectious microorganisms1 or cancer2 but sometimes, of herpesvirus-specific clonotypes in the human T cell repertoire can remain stable over unfortunately, in the shape of life-saving graft transplantation.3 The body can also decades with minimal turnover. J Virol 87: 697-700 be tricked into mobilizing the immune response against itself, to create autoimmune 2. Haen S. P. and Rammensee H. G. (2013) The diseases. The NIH estimates that approximately 23.5 million Americans suffer from repertoire of human tumor-associated epi- topes--identification and selection of antigens 4 autoimmune disease and that the prevalence is rising.
    [Show full text]
  • Evolutionary Conservation of Pou5f3 Genomic Organization and Its
    International Journal of Molecular Sciences Article Evolutionary Conservation of pou5f3 Genomic Organization and Its Dynamic Distribution during Embryogenesis and in Adult Gonads in Japanese Flounder Paralichthys olivaceus Jinning Gao 1,2, Xubo Wang 1,* and Quanqi Zhang 1,* 1 College of Marine Life Science, Ocean University of China, Key Laboratory of Marine Genetics and Breeding, Ministry of Education, Qingdao 266003, China; [email protected] 2 Center for Developmental Cardiology, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China * Correspondence: [email protected] (X.W.); [email protected] (Q.Z.); Tel.: +86-532-8203-1806 (X.W. & Q.Z.) Academic Editor: Li Lin Received: 18 December 2016; Accepted: 17 January 2017; Published: 23 January 2017 Abstract: Octamer-binding transcription factor 4 (Oct4) is a member of POU (Pit-Oct-Unc) transcription factor family Class V that plays a crucial role in maintaining the pluripotency and self-renewal of stem cells. Though it has been deeply investigated in mammals, its lower vertebrate homologue, especially in the marine fish, is poorly studied. In this study, we isolated the full-length sequence of Paralichthys olivaceus pou5f3 (Popou5f3), and we found that it is homologous to mammalian Oct4. We identified two transcript variants with different lengths of 30-untranslated regions (UTRs) generated by alternative polyadenylation (APA). Quantitative real-time RT-PCR (qRT-PCR), in situ hybridization (ISH) and immunohistochemistry (IHC) were implemented to characterize the spatial and temporal expression pattern of Popou5f3 during early development and in adult tissues. Our results show that Popou5f3 is maternally inherited, abundantly expressed at the blastula and early gastrula stages, then greatly diminishes at the end of gastrulation.
    [Show full text]
  • NCI Annual Plan & Budget Proposal for FY 2020
    Annual Plan & Budget Proposal FOR FISCAL YEAR 2020 DIRECTOR’S MESSAGE: A TIME OF 01 GREAT HOPE AND GREAT CHALLENGE LEADING THE NATION’S PROGRESS 04 AGAINST CANCER UNDERSTANDING THE MECHANISMS 10 OF CANCER PREVENTING CANCER 20 DETECTING & DIAGNOSING CANCER 26 TREATING CANCER 32 ADVANCING PUBLIC HEALTH IN CANCER 40 STRENGTHENING THE CANCER 48 RESEARCH ENTERPRISE PROFESSIONAL JUDGMENT BUDGET PROPOSAL 56 NCI ANNUAL PLAN & BUDGET PROPOSAL FOR FISCAL YEAR 2020 Director’s Message: A Time of Great Hope and Great Challenge s director of the National Cancer Institute (NCI), I am pleased to share A our Annual Plan and Budget Proposal for Fiscal Year 2020. Having been sworn in to my position a little less than a year ago, this marks my first opportunity to present, in this form, the promising results of our country’s investments in biomedical research. This plan directs attention to areas where additional support has unique potential to improve cancer prevention, detection, and treatment. To place the plan’s focus squarely on those most likely to benefit from NCI research, we have included stories of patients. While each story is unique, they are not that different from that of Mike, a patient I treated for acute leukemia. Mike started feeling poorly in 2016, and a bone marrow biopsy revealed acute myeloid Norman E. Sharpless, M.D., with former patient Mike, whom he treated for leukemia (AML). I began his initial treatment acute leukemia in 2016. with aggressive chemotherapy, which caused difficult side effects and required him to spend As a result, patients today have better options more than a month in the hospital.
    [Show full text]
  • Whole-Genome Sequencing in Personalized Therapeutics
    nature publishing group STATE ART Whole-Genome Sequencing in Personalized Therapeutics P Cordero1 and EA Ashley2 Eleven years since the initial drafts of the human genome were published, we have begun to see the first examples of the application of whole-genome sequencing to personalized diagnosis and therapeutics. The exponential decline in sequencing costs and the constant improvement in these technologies promise to further advance the use of a patient’s full genetic profile in the clinic. However, realizing the potential benefit of such sequencing will require a concerted effort by science, medicine, law, and management. In this review, we discuss current approaches to decoding the 6 billion– letter genetic code of a whole genome in a clinical context, give current examples of translating this information into therapy-guiding knowledge, and list the challenges that will need to be surmounted before these powerful data can be fully exploited to forward the goals of personalized medicine. INTRODUCTION GWAS have provided the first glimpse of the power of large- In 1990, after decades of considerable advancements in nucleic scale genetic studies and the statistical and interpretational acids research sparked by the birth of recombinant DNA tech- challenges that arise therein—characteristics that contrast with niques, the US Department of Energy announced a bold and ambi- those of traditional linkage studies.4,5 GWAS have revealed tious project with a goal of sequencing, in nucleotide resolution, associations between traits and common single-nucleotide the entirety of the human genome. The resulting cascade of events genotypes in certain populations. In the area of pharmacog- that eventually spread the use of genomics in the biological and enomics, large-scale efforts have pinpointed loci important for medical sciences is well known.
    [Show full text]